title: A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes.
abstract: Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.
authors.affiliation: Centre of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: N F
authors.initials: NF
authors.lastname: Magitta
authors.forename: A S
authors.initials: AS
authors.lastname: Bøe Wolff
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: B
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: K-M
authors.initials: KM
authors.lastname: Myhr
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
authors.forename: G
authors.initials: G
authors.lastname: Joner
authors.forename: P R
authors.initials: PR
authors.lastname: Njølstad
authors.forename: T K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Ø
authors.initials: Ø
authors.lastname: Førre
authors.forename: P M
authors.initials: PM
authors.lastname: Knappskog
authors.forename: E S
authors.initials: ES
authors.lastname: Husebye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000224:Addison Disease / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070576:NLR Proteins; D009664:Norway; D016366:Open Reading Frames / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human